The overall objective of this proposed research is to characterize the metabolic effects of 2-chloropropionate and to investigate the possible use of this compound in the treatment of hyperglycemia, lactice acidosis, and hyperlipoproteinemia. Studies will be conducted with isolated hepatocytes, perfused rat heart, isolated kidney tubules, isolated adipocytes, microsomes, and a partially purified enzyme system. In addition, an intact rat model with cannulae in the left femoral artery and vein will be used. The specific aims include: (a) to further examine the effects of 2-chloropropionate on blood glucose, lactate, pyruvate, and alanine of the 24-h fasted rat; (b) to determine the effects of 2-chloropropionate on blood glucose, lactate, pyruvate, alanine, and lipoproteins of the streptozotocin-diabetic rat; (c) to determine the acute and chronic toxicity (LD50's for the mouse) of dichloroacetate and 2-chloropropionate; (d) to determine the effects of 2-chloropropionate on gluconeogenesis, lipogenesis, ureagenesis, and fatty acid oxidation by isolated liver cells; (e) to determine whether 2-chloropropionate is effective in the treatment of lactic acidosis induced by phenformin; (f) to determine the effect of 2-chloropropionate on gluconeogenesis by the kidney cortex; (g) to determine why dichloroacetate inhibits gluconeogenesis by the kidney cortex; (h) to further characterize the enzyme(s) responsible for dehalogenation of dichloroacetate; (i) to determine whether 2-chloropropionate is dehalogenated by the liver and kidney; (j) to examine the effects of 2-chloropropionate on glucose, lactate, and fatty acid oxidation by the perfused rat hearts; and (k) to examine the effects of 2-chloropropionate on glucose utilization, lipogenesis, and lipolysis by adipocytes. Dichloroacetate lowers blood glucose but should not be used in humans because it is catabolized to oxalate. It is proposed that 2-chloropropionate can be used in place of dichloroacetate because 2-chloropropionate is an effective activator of the pyruvate dehydrogenase complex, lowers blood glucose in the fasted rat, and is not catabolized to oxalate.